Clarke’s Analytical Forensic Toxicology Clarke’s Analytical Forensic Toxicology Edited by Sue Jickells Adam Negrusz Senior Lecturer, Associate Professor of Forensic Sciences, Department of Forensic Science Assistant Director of Forensic Sciences, & Drug Monitoring, and the Director of Animal Forensic King’s College London, Toxicology Laboratory, London, Department of Biopharmaceutical Sciences, UK College of Pharmacy, University of Illinois at Chicago, USA This book is adapted from contributions published in Volume 1 of Clarke’s Analysis of Drugs and Poisons3rdedition. Consulting Editors: Anthony C Moffat M David Osselton Brian Widdop Head of the Centre Director, Consultant Toxicologist, for Pharmaceutical Analysis, Centre for Forensic Sciences, Medical Toxicology Unit, The School of Pharmacy, Bournemouth University, Guy’s Hospital, University of London, UK London, UK UK London •Chicago Published by the Pharmaceutical Press An imprint of RPS Publishing 1 Lambeth High Street, London SE1 7JN, UK 100 South Atkinson Road, Suite 200, Grayslake, IL 60030-7820, USA © Pharmaceutical Press 2008 is a trade mark of RPS Publishing RPS Publishing is the publishing organisation of the Royal Pharmaceutical Society of Great Britain First published 2008 Typeset by J&L Composition Ltd, Filey, North Yorkshire Printed in Great Britain by Cambridge University Press, Cambridge ISBN 978 0 85369 705 3 All rights reserved. No part of this publication may be repro- duced, stored in a retrieval system, or transmitted in any form or by any means, without the prior written permission of the copyright holder. The publisher makes no representation, express or implied, with regard to the accuracy of the information contained in this book and cannot accept any legal responsibility or liability for any errors or omissions that may be made. The right of Sue Jickells and Adam Negrusz to be identified as the editors of this work has been asserted by them in accordance with the Copyright, Designs and Patents Act, 1988. A catalogue record for this book is available from the British Library. Contents Preface xii Contributors xiv About the editors xvi Abbreviations xviii 1 Introduction to forensic toxicology 1 AC Moffat, M D Osselton, B Widdop, S Jickells and ANegrusz Introduction 1 Principles of forensic toxicology 2 Range of cases submitted 4 Case investigation 5 Classification of poisons 7 Samples 8 Sample analysis 8 Conclusions 10 References 10 Further reading 11 2 Pharmacokinetics and metabolism 13 O H Drummer Introduction 13 Basic concepts of pharmacokinetics 13 Drug metabolism 22 Adverse drug interactions and pharmacogenetics 29 Drug concentration and pharmacological response 34 Postmortem redistribution 36 Interpretation 36 Further reading 41 3 Drugs of abuse 43 LAKing, S D McDermott, S Jickells and ANegrusz Introduction 43 Commonly abused drugs 44 Analysis of seized drugs 58 vi Contents Clandestine laboratories 68 Analysis of the main drugs of abuse 68 Conclusion 77 References 77 4 Other substances encountered in clinical and forensic toxicology 79 R J Flanagan, M Kala, R Braithwaite and F Ade Wolff General introduction 79 Volatile substances 80 Pesticides 90 Metals and anions 101 Natural toxins 116 Summary 129 References 129 5 Workplace drug testing 135 M Peat Introduction 135 Evolution of workplace testing in the USA 136 Regulatory process in the USA 136 Proposed changes to the HHS Guidelines 141 Adulterated and substituted specimens 143 Collection of specimens 145 Role of the medical review officer 146 References 150 6 Alternative specimens 153 PKintz, V Spiehler and ANegrusz Introduction 153 Hair analysis 153 Drugs in oral fluid 165 Detection of drugs in sweat 181 References 183 Further reading 189 7 Postmortem toxicology 191 G R Jones Introduction 191 Specimens and other exhibits 191 Analytical toxicology 198 Interpretation of postmortem toxicology results 207 Summary 216 References 216 Further reading 217 Contents vii 8 Clinical toxicology, therapeutic drug monitoring, in uteroexposure to drugs of abuse 219 D R AUges, M Hallworth, C Moore and ANegrusz Introduction 219 Clinical toxicology 219 Therapeutic drug monitoring 237 In uteroexposure to drugs of abuse 256 References 260 Further reading 260 9 Drug abuse in sport 263 D ACowan, E Houghton and S Jickells Introduction 263 Rules 264 Reported analytical findings 267 Sampling 271 Analytical approach 273 Confirmatory methods 277 References 281 10 Drug-facilitated sexual assault 287 ANegrusz and R E Gaensslen Introduction and basic terms 287 The extent of the problem 288 History and legislation 289 Drugs used to facilitate sexual assault 290 Specimens and analytical methods 296 Summary 297 References 297 Further reading 298 11 Alcohol, drugs and driving 299 B K Logan, R G Gullberg, ANegrusz and S Jickells Introduction 299 Alcohol and driving 308 Drugs and driving 317 References 321 12 Forensic chemistry and solid dosage form identification 323 J Ramsey Introduction 323 Dosage forms 324 Examination of unknown products 331 References 333 viii Contents 13 Colour tests and thin-layer chromatography 335 W Jeffery and C F Poole Introduction 335 Colour tests 335 Thin layer chromatography 343 References 372 Further reading 372 14 Immunoassays 375 C Hand and D Baldwin Introduction 375 Basic principles of immunoassay 377 Heterogeneous immunoassays 382 Homogeneous immunoassays 386 Automation of immunoassay 388 Analysis of alternative samples to urine 388 Quality control, calibration, standardisation and curve fitting 389 References 391 15 Ultraviolet, visible and fluorescence spectrophotometry 393 J Cordonnier and J Schaep Introduction and theoretical background 393 UV and visible spectrophotometry 394 Instrumentation 399 Instrument performance checks 401 Sample preparation and presentation 402 Data processing and presentation of results 404 Interpretation of spectra and qualitative analysis 407 Quantitative analysis 410 Fluorescence spectrophotometry 411 Instrumentation 414 Instrument performance checks 415 Sample preparation and presentation 416 Data processing and presentation of results 416 Interpretation of spectra and qualitative analysis 417 Quantitative analysis 418 References 419 Collections of data 419 Further reading 420 16 Infrared spectroscopy 421 ADrake (with ‘Near infrared’ by R D Jee) Introduction 421 Instrumentation 425 Contents ix Data processing 428 Instrument calibration 429 Sample preparation 431 Sample presentation 432 Interpretation of spectra 441 Qualitative analysis 442 Quantitative analysis 447 Collections of data 447 Near infrared 448 References 453 Further reading 454 17 Raman spectroscopy 455 D E Bugay and PAMartoglio Smith Introduction and theory 455 Instrumentation 457 Coupled techniques 459 Data processing and presentation of results 459 System suitability tests 460 Sample preparation and sample presentation 461 Interpretation of spectra 462 Qualitative analysis 464 Quantitative analysis 466 Collections of data 467 References 468 Further reading 468 18 Gas chromatography 469 S Dawling, S Jickells and ANegrusz Introduction 469 Gas chromatography columns 470 Inlet systems 483 Detector systems 493 Specimen preparation 498 Quantitative determinations 505 Optimising operation conditions to customise applications 506 Specific applications 508 References 510 Further reading 511 19 High-performance liquid chromatography 513 TKupiec, M Slawson, F Pragst and M Herzler Introduction 513 Practical aspects of HPLC theory 514 Hardware 515